This poster by Diane Munzenmaier about RGD's new Physiological Pathways Portal was presented at the December 2009 Rat Genomics and Models meeting at Cold Spring Harbor Laboratory.

1. The Physiological Pathways Portal:
A new interactive online tool providing efficient access to genomic and
phenomic information through biological pathway analysis
Diane H. Munzenmaier, Melinda Dwinell, Victoria Petri, Mary Shimoyama, and Howard J. Jacob
Department of Physiology, Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin
Abstract PHENOTYPE DATA
Aim: The Rat Genome Database (RGD, http://rgd.mcw.edu) has been developing tools and resources to aid investigators in
the integration of genotype and phenotype data derived from rat research for the past 10 years. The new Physiological
Pathway Portal consists of navigational hubs which allow physiologists to easily link phenotype and genotype data through
intuitive mechanistic pathway flowcharts.
GENES
Methods: RGD has always contained valuable information for physiologists, however the focus has been primarily on
genomic data, making it somewhat challenging for physiologists to navigate. The Physiological Pathway diagrams provide a
familiar map for the user, including links to relevant genotype and phenotype data through flowcharts depicting related
physiological and regulatory mechanisms and pathways. Additionally, pharmacological actions and drug‐gene interactions
that influence these pathways are depicted within the diagrams and also link to related phenotype and genotype data. The
diagrams are also linked to reports for individual genes involved in any of the pathways. In addition, links from the diagram to
phenotype data allow the user to compare physiological measurements across multiple rat strains under a variety of
experimental conditions or to access strain‐specific variation data such as SNPs and other polymorphisms for direct linkage of
the genotype and phenotype data. Examples of the types of pathways included in this portal are varied and complex
regulatory and physiological systems such as blood pressure regulation, hematopoiesis and angiogenesis.
Conclusion: The new Physiological Pathways Portal at RGD promises to be an effective and user‐friendly means to access and
retrieve physiological and genomic data for researchers who use the rat as a model to study specific physiological processes
and pharmacological modulation of these processes.
Physiological Pathways are graphical depictions of multi‐organ biological processes that Genes. Gene symbols will link to their specific gene reports where the user can access
extensive genotype data and annotations on the gene in rat as well as species comparisons in
provide the user with a systems biology approach to RGD. Physiologists will find the mouse and human.
Physiological Pathways logically organized making it easy to locate and access pertinent Phenotypes & Models. Clicking on discrete functional steps in the process takes the user to the associated page
information. Discrete steps within each process are arranged temporally and regionally with of the new Phenotypes & Models tool where specific values for related phenotypes can be accessed.
organ/tissue location of each step indicated by symbol and text label for clarity. Each
pathway consists of clickable elements leading to information regarding genes involved in the
process, experimental data at specific points in the process, associated diseases due to
dysfunction of a step in the process, genetic strains that have been characterized as disease
models, drugs classes that can favorably or adversely affect the process, and associated
MOLECULAR PATHWAYS
Antidiuretic hormone (ADH) / vasopressin (AVP) regulation of blood volume
intracellular pathways. through aquaporin2 (AQP2) mediated renal water reabsorption
Associated Diseases
• diabetes insipidus
• inappropriate ADH secretion
Aortic arch, Renal collecting duct:
carotid sinus, atrial Hypothalamus basolateral membrane
baroreceptors
Drug Classes Decreased blood volume Decreased vagal input
• vasopressin agonists unloads low pressure causes disinhibition of tonic Binding of ADH/AVP to V2
• vasopressin antagonists baroreceptors causing suppression causing receptor (AVP2R) on
decreased firing of vagal increased ADH/AVP release basolateral membrane of
afferents from posterior pituitary principal cells
DISEASES
Strains and Models
• Brattleboro (LE:di/di)
Renal collecting duct: Renal collecting duct: Renal collecting duct:
• M520 (di/di)
intracellular apical membrane apical membrane
• Roman High Avoidance (RHA:di/di)
Phosphorylation of proteins
V2 receptor mediated Gs that mediate trafficking and Increased density of
protein activation, adenylyl fusion of aquaporin 2 aquaporin channels in the
cyclase stimulation , cAMP (AQP2)‐containing vesicles apical membrane increases
generation and protein to apical membrane by water permeability of
kinase A activation exocytosis collecting duct
Molecular Pathways. Steps that consist of specific complex signaling pathways are linked to RGD’s Pathways tool to allow
the user to drill down further to access information on the individual molecular signaling components of the pathways.
SIGNALING PATHWAYS Conclusion
The new Physiological Pathways portal serves as a gateway into RGD for
researchers in the biological sciences searching for gene function annotation
Diseases. The sidebar of each physiological pathway contains useful links to information associated
with the pathway. For instance, diseases known to be associated with dysfunction of a step or
and links to information regarding genotypes, phenotypes and disease
steps in the pathway are listed and link to the appropriate RGD disease ontology reports. associations. It is organized in a systems biology context through sequential
DRUGS temporal and regional steps in physiological processes with links to gene
MODELS reports, phenotype data, intracellular molecular pathways. The genetics
researcher will also find it a valuable resource for determining the functional
aspects and potential interactions of a particular gene of interest. New
pathways will continually be added on a regular basis.
Physiological Pathways seamlessly ties together many of the best features of
RGD into a functionally coherent access point making it easier and more
efficient than ever to navigate through the diverse but extensive wealth of
genomic and phenomic information that is RGD.
Signaling pathways. Steps that consist of classic second messenger intracellular signaling
Drugs. The sidebar lists generic classes of pharmaceuticals that are used in rat research and clinically. The pathways link to RGD’s existing Pathways tool to give the user a closer look.
classes link to the PharmGKB (www.pharmgkb.org) website where information on specific drugs in each
Models. The sidebar also indicates specific strains that have been characterized as suitable rat research RGD is funded by NIH 5R01HL064541
models for diseases associated with the physiological pathway of interest. These strain names link to
class can be found. their strain report pages in RGD.